Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections.
...To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP.
A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups.
Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness.
The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed.
Among 2862 randomized participants (mean SD age, 43 11.5 years; 2369 82.8%) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, 95% CI, -0.5% to 2.5%; P = .18) (adjusted odds ratio OR, 1.18 95% CI, 0.95-1.45). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons 95% CI, -48.2 to 4.4; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, 95% CI, -33.3 to 15.4; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons 95% CI, -28.2 to 10.9; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons 95% CI, -23.8 to 1.3; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group.
Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza.
ClinicalTrials.gov Identifier: NCT01249625.
The outbreak of 2019 novel coronavirus (COVID‐19) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries ...and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found clinically that very few patients were diagnosed with both COVID‐19 and influenza virus. A total of 5 of the 115 patients confirmed with COVID‐19 were also diagnosed with influenza virus infection, with three cases being influenza A and two cases being influenza B. In this study, we describe the clinical characteristics of those patients who got infected with COVID‐19 as well as influenza virus. Common symptoms at onset of illness included fever (five 100% patients), cough (five 100% patients), shortness of breath (five 100% patients), nasal tampon (three 60% patients), pharyngalgia (three 60% patients), myalgia (two 40% patients), fatigue (two 40% patients), headache (two 40% patients), and expectoration (two 40% patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (four 80% patients), and liver functions alanine aminotransferase and aspartate aminotransferase (two 40% patients and two 40% patients) and C‐reactive protein (four 80% patients) were increased when admitted to hospital. They stayed in the hospital for 14, 30, 17, 12, and 19 days (28.4 ± 7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (one 20% patients), acute liver injury (three 60% patients), and diarrhea (two 40% patients). All patients were given antiviral therapy (including oseltamivir), oxygen inhalation, and antibiotics. Three patients were treated with glucocorticoids including two treated with oral glucocorticoids. One of the five patients had transient hemostatic medication for hemoptysis. Fortunately, all patients did not need intensive care unit and were discharged from the hospital without death. In conclusion, those patients with both COVID‐19 and influenza virus infection did not appear to show a more severe condition because based on the laboratory findings, imaging studies, and patient prognosis, they showed similar clinical characteristics as those patients with COVID‐19 infection only. However, it is worth noting that the symptoms of nasal tampon and pharyngalgia may be more prone to appear for those coinfection patients.
To investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective ...observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19).
A retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February–20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019–2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed.
A total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0–5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low.
We found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.
Pigs are considered as important hosts or “mixing vessels” for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and ...preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.
•Refusal rate of nurses to influenza vaccine reduced during the pandemic.•A low acceptance level and high hesitancy level to COVID vaccination was observed.•A strong association between COVID-19 and ...influenza vaccine acceptance was found.•Major concern of nurses about the COVID-19 vaccine was its efficacy and safety.
Maintaining health of healthcare workers with vaccination is a major component of pandemic preparedness and acceptance of vaccinations is essential to its success. This study aimed to examine impact of the coronavirus disease 2019 (COVID-19) pandemic on change of influenza vaccination acceptance and identify factors associated with acceptance of potential COVID-19 vaccination.
A cross-sectional self-administered anonymous questionnaire survey was conducted among nurses in Hong Kong, China during 26 February and 31 March 2020. Their previous acceptance of influenza vaccination and intentions to accept influenza and COVID-19 vaccination were collected. Their relationship with work-related and other factors were examined using multiple multinomial logistic regressions.
Responses from 806 participants were retrieved. More nurses changed from vaccination refusal to hesitancy or acceptance than those changed from acceptance to vaccination hesitancy or refusal (15.5% vs 6.8% among all participants, P < 0.001). 40.0% participants intended to accept COVID-19 vaccination, and those in private sector (OR: 1.67, 95%CI: 1.11–2.51), with chronic conditions (OR: 1.83, 95%CI: 1.22–2.77), encountering with suspected or confirmed COVID-19 patients (OR: 1.63, 95%CI: 1.14–2.33), accepted influenza vaccination in 2019 (OR: 2.03, 95%CI: 1.47–2.81) had higher intentions to accept it. Reasons for refusal and hesitation for COVID-19 vaccination included “suspicion on efficacy, effectiveness and safety”, “believing it unnecessary”, and “no time to take it”.
With a low level of COVID-19 acceptance intentions and high proportion of hesitation in both influenza and COVID-19 vaccination, evidence-based planning are needed to improve the uptake of both vaccinations in advance of their implementation. Future studies are needed to explore reasons of change of influenza vaccination acceptance, look for actual behaviour patterns of COVID-19 vaccination acceptance and examine effectiveness of promotion strategies.
COVID‐19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The ...present study aimed to analyze the characteristics of severe COVID‐19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID‐19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID‐19, the lymphocytes in the severe COVID‐19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C‐reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = −.37; P < .01) was negatively correlated with the CT severity scores. The receiver‐operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID‐19 was 0.87 (95% CI 0.10–1.00) at 20.42 mg/L cut‐off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID‐19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID‐19.
Highlights
Compared with COVID’19, Patients with flu had higher WBC and granulocyte.
Lymphocyte progressively decreased in the progress of COVID’19.
CRP level associated with CT scores and disease development of COVID’19.
CRP increased at the initial stage of severe COVID’19, prior to CT findings.
CRP showed good performance in prediction of severe COVID’19.
Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described ...as a “cytokine storm,” associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33—amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.
Despite decades of surveillance and pharmaceutical and non-pharmaceutical interventions, seasonal influenza viruses continue to cause epidemics around the world each year. The key process underlying ...these recurrent epidemics is the evolution of the viruses to escape the immunity that is induced by prior infection or vaccination. Although we are beginning to understand the processes that underlie the evolutionary dynamics of seasonal influenza viruses, the timing and nature of emergence of new virus strains remain mostly unpredictable. In this Review, we discuss recent advances in understanding the molecular determinants of influenza virus immune escape, sources of evolutionary selection pressure, population dynamics of influenza viruses and prospects for better influenza virus control.
Summary Background The avian influenza A H7N9 virus has caused infections in human beings in China since 2013. A large epidemic in 2016–17 prompted concerns that the epidemiology of the virus might ...have changed, increasing the threat of a pandemic. We aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of patients infected with A H7N9 in the 2016–17 epidemic compared with previous epidemics. Methods In this epidemiological study, we obtained information about all laboratory-confirmed human cases of A H7N9 virus infection reported in mainland China as of Feb 23, 2017, from an integrated electronic database managed by the China Center for Disease Control and Prevention (CDC) and provincial CDCs. Every identified human case of A H7N9 virus infection was required to be reported to China CDC within 24 h via a national surveillance system for notifiable infectious diseases. We described the epidemiological characteristics across epidemics, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital for routine clinical practice rather than for isolation purpose. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge using survival analysis techniques. Findings Between Feb 19, 2013, and Feb 23, 2017, 1220 laboratory-confirmed human infections with A H7N9 virus were reported in mainland China, with 134 cases reported in the spring of 2013, 306 in 2013–14, 219 in 2014–15, 114 in 2015–16, and 447 in 2016–17. The 2016–17 A H7N9 epidemic began earlier, spread to more districts and counties in affected provinces, and had more confirmed cases than previous epidemics. The proportion of cases in middle-aged adults increased steadily from 41% (55 of 134) to 57% (254 of 447) from the first epidemic to the 2016–17 epidemic. Proportions of cases in semi-urban and rural residents in the 2015–16 and 2016–17 epidemics (63% 72 of 114 and 61% 274 of 447, respectively) were higher than those in the first three epidemics (39% 52 of 134, 55% 169 of 306, and 56% 122 of 219, respectively). The clinical severity of individuals admitted to hospital in the 2016–17 epidemic was similar to that in the previous epidemics. Interpretation Age distribution and case sources have changed gradually across epidemics since 2013, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection with A H7N9 virus. Funding The National Science Fund for Distinguished Young Scholars.
Lambda interferons (IFNλs) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique ...non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFNλs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology. Central to this are neutrophils which respond to both cytokines to upregulate antimicrobial functions but exhibit pro-inflammatory activation only to type I IFNs. Accordingly, Ifnlr1−/− mice display enhanced type I IFN production, neutrophilia, lung injury, and lethality, while therapeutic administration of PEG-IFNλ potently suppresses these effects. IFNλs therefore constitute the front line of antiviral defense in the lung without compromising host fitness.
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•IFNλs are the first IFNs produced that suppress initial viral spread•IFNλs exhibit potent antiviral functions without activating inflammation•Type I IFNs come up later to enhance antiviral and pro-inflammatory responses•IFNλs and type I IFNs ensure optimal viral clearance with minimal collateral damage
The importance of IFNλs in the respiratory tract remains puzzling. Galani and colleagues show that IFNλs provide front-line antiviral protection without activating inflammation. When infection escapes IFNλ control, type I IFNs come into play to enhance antiviral defenses and trigger pro-inflammatory responses essential for confronting infection but causing immunopathology.
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